A major aim of the applicant's research over the past 20 years has been to determine the extent to which exercise-training can compensate for and/or partially reverse the deterioration in cardiovascular, neuromuscular, and metabolic functions and in physical performance capacities that occur with advancing age. As a result of this research, and that of others, there is, according to the applicant, now sufficient information regarding the beneficial effects of exercise in late middle- age and early old-age to justify promotion of exercise for maintenance of functional capacity in this age group. The applicant has, therefore, decided to focus the research of the OAIC on the question of whether or not physical frailty is reversible in old women and men at risk of losing their independence. There are two intervention studies (IS) in this OAIC. The goals of IS-1 are a) to determine the extent to which trail old women and men can respond to exercise training with the adaptations that have been shown to occur in younger individuals, and b) to assess whether the adaptations to exercise in the frail elderly are sufficiently large and functionally important to result in a significant reversal of frailty. The intervention in IS-1 is a 3-phase exercise program; the first phase consists of physical therapy exercises, the second consists of weight training exercises and the third consists of endurance exercise; the second and third phases will be superimposed on maintenance programs of the preceding types of exercise. The aim is to test the hypotheses that exercise can: a) increase functional capacity and reduce physical frailty; b) improve aerobic exercise capacity and/or cardiovascular function; c) induce a sufficient increase in muscle protein synthesis and/or decrease in muscle protein breakdown to result in increases in lean body and skeletal muscle mass; d) increase bone quantity and/or quality; and e) decrease insulin resistance, improve glucose tolerance, and improve lipid and lipoprotein levels. To the extent that it is feasible, the plan is to examine the mechanisms by which improvements in function are mediated. The interventions in IS-2 are hormone replacement therapy (HRT) and exercise superimposed on HRT. The goals of IS-2 are to determine whether a) HRT can bring about a reduction of frailty in physically frail old women, and b) exercise training results in greater improvements in functional capacity, muscle mass, cardiovascular function, and bone quantity and quality, in women who have been on HRT for 9-month than in sex hormone deficient women. The research of IS-1 and IS-2, and the pilot studies will be supported by five Research Resource Cores (RRC): Recruitment/Assessment/Health Services; Functional Assessment; Clinical Physiology/ Pathophysiology; Metabolic Function/Body Composition; and Biostatistics/Data Management. A long-term goal is to obtain information that can be used to design practical, individualized programs of exercise that can be utilized in community settings to prevent or reverse physical frailty and maintain functional independence. To translate findings from this research into health care practice, the Demonstration and Information Dissemination Core will disseminate research findings that are relevant to the prevention and reversal of frailty to the public and health care professionals. A major goal of the Research Development Core is to utilize the OAIC research activities and RRCs to train new investigators from a variety of disciplines to perform gerontological research relevant to the goals of the OAIC.